College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi 030801, China; Shanxi Key Laboratory of Ecological Animal Sciences and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Toxicology. 2022 Apr 30;472:153192. doi: 10.1016/j.tox.2022.153192. Epub 2022 Apr 27.
Bisphenol-A (BPA), a well-known estrogenic endocrine disruptor, is generally applied to turn out plastic consumer products. Available data have manifested that exposure to BPA can trigger insulin resistance. Hence, the purpose of the actual study was to consider the impacts of BPA exposure on cognitive function and insulin signaling pathway in the hippocampus of male offspring mice. For this purpose, the pregnant female mice were treated either vehicle (0.1% ethanol) or BPA (0.01, 0.1, and 1 µg/mL) via drinking water from day 1 of gestation until delactation (D1-PND21, newborn exposure). Afterward, the three-week-old male offspring mice took orally with the same doses of BPA for nine weeks (PND84). The behavioral tests, blood sugar level, histological observation, transcriptome sequencing, glucose transporter 4 (GLUT4), and hippocampal insulin signaling pathway were checked for the male offspring mice at 13 weeks of age (PND91). Our data indicated that BPA exposure impaired cognitive function, disrupted the hippocampal regular cell arrangement, increased blood glucose levels, disturbed the insulin signaling pathway including phosphorylated insulin receptor substrate1 (p-IRS1), protein kinase B (p-AKT), and glycogen synthase kinase 3β (p-GSK3β). At the same time, the mRNA and protein expressions of GLUT4 were markedly down-regulated in the BPA-exposed groups. To sum up, it has been suggested from these results that BPA has detrimental effects on the insulin signaling pathway, which might subsequently be conducive to the impairment of cognitive function in the adult male offspring mice. Therefore, BPA exposure might in part be an element of risk for the long-term neurodegeneration in male offspring mice.
双酚 A（BPA）是一种众所周知的雌激素内分泌干扰物，通常用于生产塑料消费品。现有数据表明，接触 BPA 会引发胰岛素抵抗。因此，本研究旨在探讨 BPA 暴露对雄性仔鼠海马认知功能和胰岛素信号通路的影响。为此，雌性孕鼠从妊娠第 1 天至哺乳期（D1-PND21，新生暴露）通过饮用水分别给予 vehicle（0.1%乙醇）或 BPA（0.01、0.1 和 1μg/mL）。之后，3 周龄雄性仔鼠以相同剂量的 BPA 进行 9 周的口服灌胃（PND84）。13 周龄（PND91）时，检测雄性仔鼠的行为学测试、血糖水平、组织学观察、转录组测序、葡萄糖转运蛋白 4（GLUT4）和海马胰岛素信号通路。结果表明，BPA 暴露损害了认知功能，破坏了海马的正常细胞排列，升高了血糖水平，干扰了胰岛素信号通路，包括磷酸化胰岛素受体底物 1（p-IRS1）、蛋白激酶 B（p-AKT）和糖原合成酶激酶 3β（p-GSK3β）。同时，BPA 暴露组 GLUT4 的 mRNA 和蛋白表达明显下调。总之，这些结果表明 BPA 对胰岛素信号通路有不良影响，可能导致成年雄性仔鼠认知功能受损。因此，BPA 暴露可能是雄性仔鼠长期神经退行性变的风险因素之一。
